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. 1993 Feb 15;290(Pt 1):67–73. doi: 10.1042/bj2900067

Mechanisms of hepatic phosphatidylcholine synthesis in the developing guinea pig: contributions of acyl remodelling and of N-methylation of phosphatidylethanolamine.

G C Burdge 1, F J Kelly 1, A D Postle 1
PMCID: PMC1132383  PMID: 8439299

Abstract

Hepatic phosphatidylcholine (PC) from the immature fetal guinea pig at day 55 of gestation comprised mainly unsaturated molecular species containing C18:2(n-6) and C22:6(n-3) at the sn-2 position, reflecting placental permeability to essential fatty acids. At both day 55 and term (day 68), [Me-14C]choline was incorporated in utero over 3 h largely into sn-1-C16:0 PC species, with incorporation into sn-1-C18:0 PC species increasing by 18 h of incubation. Comparison of specific radioactivities after 3 h and 18 h suggests PC acyl remodelling by phospholipase A1. No incorporation into C20:4(n-6)-containing PC species could be detected of either [Me-14C]choline in vivo or CDP-[Me-14C]choline in isolated microsomes. The major phosphatidylethanolamine (PE) species were 16:0/22:6 and 18:0/22:6. Although [14C]ethanolamine was initially incorporated mainly into sn-1-C16:0 species, specific-radioactivity analysis suggested differential turnover rather than acyl remodelling. [1,2-14C]Ethanolamine and [Me-14C]methionine incorporation into PC molecular species indicated that both newly synthesized and total PE pools were available for N-methylation. Since the PC pool synthesized from PE included C20:4- and C22:6-containing species, N-methylation may provide a mechanism for supplying essential long-chain fatty acids to developing tissues that can be regulated independently from bulk PC synthesis.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arvidson G. A. Structural and metabolic heterogeneity of rat liver glycerophosphatides. Eur J Biochem. 1968 May;4(4):478–486. doi: 10.1111/j.1432-1033.1968.tb00237.x. [DOI] [PubMed] [Google Scholar]
  2. BLIGH E. G., DYER W. J. A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959 Aug;37(8):911–917. doi: 10.1139/o59-099. [DOI] [PubMed] [Google Scholar]
  3. BREMER J., GREENBERG D. M. Biosynthesis of choline in vitro. Biochim Biophys Acta. 1960 Jan 1;37:173–175. doi: 10.1016/0006-3002(60)90104-9. [DOI] [PubMed] [Google Scholar]
  4. Bjørnstad P., Bremer J. In vivo studies on pathways for the biosynthesis of lecithin in the rat. J Lipid Res. 1966 Jan;7(1):38–45. [PubMed] [Google Scholar]
  5. Caesar P. A., Wilson S. J., Normand C. S., Postle A. D. A comparison of the specificity of phosphatidylcholine synthesis by human fetal lung maintained in either organ or organotypic culture. Biochem J. 1988 Jul 15;253(2):451–457. doi: 10.1042/bj2530451. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dobbing J., Sands J. Comparative aspects of the brain growth spurt. Early Hum Dev. 1979 Mar;3(1):79–83. doi: 10.1016/0378-3782(79)90022-7. [DOI] [PubMed] [Google Scholar]
  7. Dobbing J., Sands J. Growth and development of the brain and spinal cord of the guinea pig. Brain Res. 1970 Jan 6;17(1):115–123. doi: 10.1016/0006-8993(70)90311-2. [DOI] [PubMed] [Google Scholar]
  8. Dobbing J., Sands J. Quantitative growth and development of human brain. Arch Dis Child. 1973 Oct;48(10):757–767. doi: 10.1136/adc.48.10.757. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hershfield M. S., Nemeth A. M. Placental transport of free palmitic and linoleic acids in the guinea pig. J Lipid Res. 1968 Jul;9(4):460–468. [PubMed] [Google Scholar]
  10. Holub B. J., Kuksis A. Interrelationships in the metabolism of liver arachidonoyllecithins and plasma cholesteryl arachidonate in the rat. Can J Biochem. 1971 Sep;49(9):1005–1011. doi: 10.1139/o71-147. [DOI] [PubMed] [Google Scholar]
  11. Holub B. J., Kuksis A. Metabolism of molecular species of diacylglycerophospholipids. Adv Lipid Res. 1978;16:1–125. doi: 10.1016/b978-0-12-024916-9.50007-x. [DOI] [PubMed] [Google Scholar]
  12. Kishimoto Y., Davies W. E., Radin N. S. Developing rat brain: changes in cholesterol, galactolipids, and the individual fatty acids of gangliosides and glycerophosphatides. J Lipid Res. 1965 Oct;6(4):532–536. [PubMed] [Google Scholar]
  13. Lindahl M., von Schenck H., Tagesson C. Isolation and characterization of phospholipase A2 from rat lung with affinity chromatography and two-dimensional gel electrophoresis. Biochim Biophys Acta. 1989 Oct 17;1005(3):282–288. doi: 10.1016/0005-2760(89)90050-7. [DOI] [PubMed] [Google Scholar]
  14. Macdonald G., Thompson W. Different selectivities in acylation and methylation pathways of phosphatidylcholine formation in guinea pig and rat livers. Biochim Biophys Acta. 1975 Sep 19;398(3):424–432. doi: 10.1016/0005-2760(75)90193-9. [DOI] [PubMed] [Google Scholar]
  15. Mookerjea S., Park C. E., Kuksis A. Lipd profiles of plasma lipoproteins of fasted and fed normal and choline-deficient rats. Lipids. 1975 Jul;10(7):374–382. doi: 10.1007/BF02532440. [DOI] [PubMed] [Google Scholar]
  16. Ogino H., Matsumura T., Satouchi K., Saito K. Changes in molecular species of rat liver choline glycerophospholipids with development. Biochim Biophys Acta. 1980 Jun 23;618(3):431–438. [PubMed] [Google Scholar]
  17. Okuyama H., Yamada K., Ikezawa H. Accepton concentration effect in the selectivity of acyl coenzyme A: U aclglycerylphosphorylcholine acyltransferase system in rat liver. J Biol Chem. 1975 Mar 10;250(5):1710–1713. [PubMed] [Google Scholar]
  18. Parkes J. G., Thompson W. Structural and metabolic relation between molecular classes of phosphatidylcholine in mitochondria and endoplasmic reticulum of guinea pig liver. J Biol Chem. 1973 Oct 10;248(19):6655–6662. [PubMed] [Google Scholar]
  19. Pelech S. L., Vance D. E. Regulation of phosphatidylcholine biosynthesis. Biochim Biophys Acta. 1984 Jun 25;779(2):217–251. doi: 10.1016/0304-4157(84)90010-8. [DOI] [PubMed] [Google Scholar]
  20. Postle A. D. Method for the sensitive analysis of individual molecular species of phosphatidylcholine by high-performance liquid chromatography using post-column fluorescence detection. J Chromatogr. 1987 Apr 10;415(2):241–251. doi: 10.1016/s0378-4347(00)83216-8. [DOI] [PubMed] [Google Scholar]
  21. Ravel D., Chambaz J., Pepin D., Manier M. C., Bereziat G. Essential fatty acid interconversion during gestation in the rat. Biochim Biophys Acta. 1985 Jan 9;833(1):161–164. doi: 10.1016/0005-2760(85)90264-4. [DOI] [PubMed] [Google Scholar]
  22. Ridgway N. D., Vance D. E. Specificity of rat hepatic phosphatidylethanolamine N-methyltransferase for molecular species of diacyl phosphatidylethanolamine. J Biol Chem. 1988 Nov 15;263(32):16856–16863. [PubMed] [Google Scholar]
  23. Samborski R. W., Ridgway N. D., Vance D. E. Evidence that only newly made phosphatidylethanolamine is methylated to phosphatidylcholine and that phosphatidylethanolamine is not significantly deacylated-reacylated in rat hepatocytes. J Biol Chem. 1990 Oct 25;265(30):18322–18329. [PubMed] [Google Scholar]
  24. Scagnelli G. P., Cooper P. S., VandenBroek J. M., Berman W. F., Schwartz C. C. Plasma 1-palmitoyl-2-linoleoyl phosphatidylcholine. Evidence for extensive phospholipase A1 hydrolysis and hepatic metabolism of the products. J Biol Chem. 1991 Sep 25;266(27):18002–18011. [PubMed] [Google Scholar]
  25. Scott B. L., Bazan N. G. Membrane docosahexaenoate is supplied to the developing brain and retina by the liver. Proc Natl Acad Sci U S A. 1989 Apr;86(8):2903–2907. doi: 10.1073/pnas.86.8.2903. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Svennerholm L. Distribution and fatty acid composition of phosphoglycerides in normal human brain. J Lipid Res. 1968 Sep;9(5):570–579. [PubMed] [Google Scholar]
  27. Tijburg L. B., Geelen M. J., van Golde L. M. Regulation of the biosynthesis of triacylglycerol, phosphatidylcholine and phosphatidylethanolamine in the liver. Biochim Biophys Acta. 1989 Jul 17;1004(1):1–19. doi: 10.1016/0005-2760(89)90206-3. [DOI] [PubMed] [Google Scholar]
  28. Tijburg L. B., Houweling M., Geelen M. J., van Golde L. M. Effects of dietary conditions on the pool sizes of precursors of phosphatidylcholine and phosphatidylethanolamine synthesis in rat liver. Biochim Biophys Acta. 1988 Mar 4;959(1):1–8. doi: 10.1016/0005-2760(88)90143-9. [DOI] [PubMed] [Google Scholar]
  29. Tijburg L. B., Samborski R. W., Vance D. E. Evidence that remodeling of the fatty acids of phosphatidylcholine is regulated in isolated rat hepatocytes and involves both the sn-1 and sn-2 positions. Biochim Biophys Acta. 1991 Sep 11;1085(2):184–190. doi: 10.1016/0005-2760(91)90093-w. [DOI] [PubMed] [Google Scholar]
  30. Vance D. E., Ridgway N. D. The methylation of phosphatidylethanolamine. Prog Lipid Res. 1988;27(1):61–79. doi: 10.1016/0163-7827(88)90005-7. [DOI] [PubMed] [Google Scholar]
  31. Vance J. E. Compartmentalization of phospholipids for lipoprotein assembly on the basis of molecular species and biosynthetic origin. Biochim Biophys Acta. 1988 Nov 4;963(1):70–81. doi: 10.1016/0005-2760(88)90339-6. [DOI] [PubMed] [Google Scholar]
  32. Vance J. E. The use of newly synthesized phospholipids for assembly into secreted hepatic lipoproteins. Biochim Biophys Acta. 1989 Nov 6;1006(1):59–69. doi: 10.1016/0005-2760(89)90323-8. [DOI] [PubMed] [Google Scholar]
  33. Vance J. E., Vance D. E. The role of phosphatidylcholine biosynthesis in the secretion of lipoproteins from hepatocytes. Can J Biochem Cell Biol. 1985 Aug;63(8):870–881. doi: 10.1139/o85-108. [DOI] [PubMed] [Google Scholar]
  34. WIDDOWSON E. M. Chemical composition of newly born mammals. Nature. 1950 Oct 14;166(4224):626–628. doi: 10.1038/166626a0. [DOI] [PubMed] [Google Scholar]
  35. Wells I. C., Remy C. N. Choline metabolism in normal and choline-deficient rats of different ages. Arch Biochem Biophys. 1965 Oct;112(1):201–206. doi: 10.1016/0003-9861(65)90030-5. [DOI] [PubMed] [Google Scholar]
  36. Wells I. C., Remy C. N. Choline metabolism in normal and choline-deficient rats of different ages. Arch Biochem Biophys. 1965 Oct;112(1):201–206. doi: 10.1016/0003-9861(65)90030-5. [DOI] [PubMed] [Google Scholar]
  37. Yao Z. M., Vance D. E. The active synthesis of phosphatidylcholine is required for very low density lipoprotein secretion from rat hepatocytes. J Biol Chem. 1988 Feb 25;263(6):2998–3004. [PubMed] [Google Scholar]

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